一种新合成吡啶类化合物对黑质多巴胺能神经元电活动的调制作用

REGULATORY EFFECTS OF A NOVEL SYNTHESIZED PYRIDINE COMPOUND ON ELECTRICAL ACTIVITY OF DOPAMINERGIC NEURONS IN THE SUBSTANTIA NIGRA

目的研究一种新合成的吡啶类化合物对黑质多巴胺能神经元电活动的调制作用。方法应用全细胞膜片钳技术观察该化合物对黑质多巴胺能神经元自发放电频率、诱发放电、内向整流(Sag)幅度等电活动相关指标的影响。结果C57/BL6小鼠黑质脑片灌流500μmol/L化合物,多巴胺能神经元自发放电频率明显受到抑制(t=5.396,P<0.05),0~40 pA的除极电流刺激后记录的神经元诱发放电次数明显减少;给予神经元40 pA的除极电流刺激,与基础放电活动相比,峰电位间隔时间、动作电位的起始时间和时程均明显增加(t=1.920~2.558,P<0.05);与基础Sag幅度相比,-200 pA电流刺激后的Sag幅度明显减小,差异具有统计学意义(t=3.149,P<0.05)。结论此化合物能够抑制正常C57/BL6小鼠黑质多巴胺能神经元的兴奋性并降低Sag幅度,对神经元的电活动发挥调控作用。

Objective To investigate the modulatory effects of a novel synthesized pyridine compound on the electrical activity of dopaminergic neurons in the substantia nigra.Methods The whole-cell patch clamp technique was used to record the changes induced by the compound in the electrical activity of substantia nigra dopaminergic neurons(spontaneous discharge frequency,evoked firing rate,and sag amplitude).Results With C57/BL6 mouse substantia nigra slices under perfusion with the compound at a concentration of 500μmol/L,dopaminergic neurons’spontaneous firing rate was significantly decreased(t=5.396,P<0.05).The evoked firing rate was significantly reduced in response to depolarizing current pulses of 0-40 pA;in response to a depolarizing current pulse of 40 pA,the dopaminergic neurons’interspike interval and action potential’duration and initial time were significantly increased as compared with the baseline electrical activity(t=1.920-2.558,P<0.05).In response to a current pulse of-200 pA,the dopaminergic neurons exhibited a significantly lowered sag amplitude compared with the baseline sag amplitude(t=3.149,P<0.05).Conclusion The novel synthesized compound could inhibit the excitability and decrease the sag amplitude of substantia nigra dopaminergic neurons in normal C57/BL6 mice,with a regulatory effect on the electrical activity of neurons.